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United States Patent |
6,015,919
|
Pugin
|
January 18, 2000
|
Dihalogenated ferrocenes and processes for the preparation thereof
Abstract
The invention relates to a compound of formula I
##STR1##
R.sub.1 is C.sub.1 -C.sub.8 alkyl, phenyl or phenyl substituted by from 1
to 3 C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy substituents;
R.sub.2 and R.sub.3 are each independently of the other hydrogen or C.sub.1
-C.sub.12 alkyl; and
Hal is F, Cl, Br or I.
Compounds of formula I are valuable intermediates for compounds of formula
III which are also a subject of this invention:
##STR2##
R.sub.1, R.sub.2, R.sub.3 and Hal are as defined above; R.sub.10 and
R.sub.11 are identical or different and are C.sub.1 -C.sub.12 alkyl,
C.sub.5 -C.sub.12 cycloalkyl, phenyl, C.sub.5 -C.sub.12 cycloalkyl
substituted by C.sub.1 -C.sub.4 alkyl or by C.sub.1 -C.sub.4 alkoxy, or
phenyl substituted by from one to three C.sub.1 -C.sub.4 alkyl, C.sub.1
-C.sub.4 alkoxy, --SiR.sub.4 R.sub.5 R.sub.6, halogen, --SO.sub.3 M,
--CO.sub.2 M, --PO.sub.3 M, --NR.sub.7 R.sub.8, --[.sup.+ NR.sub.7 R.sub.8
R.sub.9 ]X.sup.- or C.sub.1 -C.sub.5 fluoroalkyl substituents; or
the group --PR.sub.10 R.sub.11 is a radical of formula IV, IVa, IVb or IVc
##STR3##
R.sub.4, R.sub.5 and R.sub.6 are each independently of the others C.sub.1
-C.sub.12 alkyl or phenyl;
R.sub.7 and R.sub.8 are H, C.sub.1 -C.sub.12 alkyl or phenyl or R.sub.7 and
R.sub.8 together are tetramethylene, pentamethylene or
3-oxa-1,5-pentylene;
R.sub.9 is H or C.sub.1 -C.sub.4 alkyl;
M is H or an alkali metal;
X.sup.- is the anion of a monobasic acid.
Inventors:
|
Pugin; Benoit (Munchenstein, CH)
|
Assignee:
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Novartis AG (Basel, CH)
|
Appl. No.:
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246203 |
Filed:
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February 8, 1999 |
Foreign Application Priority Data
Current U.S. Class: |
556/145; 502/152; 502/154; 556/143; 556/144 |
Intern'l Class: |
C07F 017/02; C07B 031/00 |
Field of Search: |
556/14,11,13,143,144,145
|
References Cited
U.S. Patent Documents
5244857 | Sep., 1993 | Pugin et al. | 502/167.
|
5252751 | Oct., 1993 | Pugin et al. | 549/214.
|
5371256 | Dec., 1994 | Togni et al. | 556/14.
|
5466844 | Nov., 1995 | Spindler et al. | 556/11.
|
5583241 | Dec., 1996 | Spindler | 556/143.
|
5627293 | May., 1997 | Pugin | 556/11.
|
5783715 | Jul., 1998 | Pugin | 556/11.
|
5925778 | Jul., 1999 | Pugin | 556/144.
|
Foreign Patent Documents |
9632400 | Oct., 1996 | WO.
| |
9702232 | Jan., 1997 | WO.
| |
Other References
Achiwa, K., "Catalytic Asymmetric Hydrogenations with Polymer Supported
Chiral Pyrrolidinephosphine-Rhodium Complexes," Chemistry Letters, 1978,
pp. 905-908.
Cullen et al., "Polymer Supported Ferrocene Derivatives. Catalytic
Hydrosilylation of Olefins by Supported Palladium and Platinum Complexes,"
J. of Organom. Chem., vol. 333, 1987, pp. 269-280.
Kim et al., "Functionalized Organometallic Ligand (1) Synthesis of Some
Ferrocene Derivatives of Cyclohexyl-and Cyclopentadienyl-phosphines,"
Bull. Korean Chem. Soc., vol. 13, No. 6, 1992, pp. 588-592.
Kovar et al., "A Convenient Route to 1'1'-Dihalogenated Ferrocenes",
Organometallics in Chemical Synthesis, vol. 1 1970/1971, pp. 173-181.
Togni, A., "Developing New Chiral Ferrocenyl Ligands for Asymmetric
Catalysis: A Personal Account," Chimia, vol. 50, 1996, pp. 86-93.
|
Primary Examiner: Shah; Mukund J.
Assistant Examiner: Sripada; Pavanaram K
Attorney, Agent or Firm: Kalinchak; Stephen G., Lopez; Gabriel
Parent Case Text
This application is a divisional of U.S. application Ser. No. 08/930,171,
filed Oct. 9, 1997 now U.S. Pat. No. 5,925,778. The entire contents of the
'171 application are incorporated herein by reference.
Claims
What is claimed is:
1. A compound of formula III
##STR30##
R.sub.1 is C.sub.1 -C.sub.8 alkyl, phenyl or phenyl substituted by from 1
to 3 C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy substituents;
R.sup.2 and R.sup.3 are each independently of the other hydrogen or C.sub.1
-C.sub.12 alkyl; and
Hal is F, Cl, Br or I;
R.sub.10 and R.sub.11 are identical or different and are C.sub.1 -C.sub.12
alkyl, C.sub.5 -C.sub.12 cycloalkyl, phenyl, C.sub.5 -C.sub.12 cycloalkyl
substituted by C.sub.1 -C.sub.4 alkyl or by C.sub.1 -C.sub.4 alkoxy, or
phenyl substituted by from one to three C.sub.1 -C.sub.4 alkyl, C.sub.1
-C.sub.4 alkoxy, --SiR.sub.4 R.sub.5 R.sub.6, halogen, --SO.sub.3 M,
--CO.sub.2 M, --PO.sub.3 M, --NR.sub.7 R.sub.8, --(.sup.+ NR.sub.7 R.sub.8
R.sub.9)X.sup.- or C.sub.1 -C.sub.5 fluoroalkyl substituents; or
the group --PR.sub.10 R.sub.11 is a radical of formula IV, IVa, IVb, or IVc
##STR31##
R.sub.4, R.sub.5 and R.sub.6 are each independently of the others C.sub.1
-C.sub.12 alkyl or phenyl;
R.sub.7 and R.sub.8 are H, C.sub.1 -C.sub.12 alkyl or phenyl or R.sub.7 and
R.sub.8 together are tetramethylene, pentamethylene or
3-oxa-1,5-pentylene;
R.sub.9 is H or C.sub.1 -C.sub.4 alkyl;
M is H or an alkali metal;
X.sup.- is the anion of a monobasic acid.
2. A compound of formula III according to claim 1, wherein R.sub.10 and
R.sub.11 as alkyl are C.sub.1 -C.sub.8 alkyl.
3. A compound of formula III according to claim 1, wherein R.sub.10 and
R.sub.11 as cycloalkyl contain from 5 to 8 carbon atoms.
4. A compound of formula III according to claim 1, wherein R.sub.10 and
R.sub.11 are unsubstituted phenyl or phenyl substituted by 1 or 2
substituents.
5. A compound of formula III according to claim 1, wherein R.sub.10 and
R.sub.11 as substituted phenyl are 2-methyl-, 3-methyl-, 4-methyl-, 2- or
4-ethyl-, 2- or 4-isopropyl-, 2- or 4-tert-butyl-, 2-methoxy-, 3-methoxy-,
4-methoxy-, 2- or 4-ethoxy-, 4-trimethylsilyl-, 2- or 4-fluoro,
2,4-difluoro-, 2- or 4-chloro-, 2,4-dichloro-, 2,4-dimethyl-,
3,5-dimethyl-, 2-methoxy-4-methyl-, 3,5-dimethyl-4-methoxy-,
3,5-dimethyl-4-(dimethylamino)-, 2- or 4-amino-, 2- or 4-methylamino-, 2-
or 4-(dimethylamino)-, 2- or 4-SO.sub.3 H--, 2- or 4-SO.sub.3 Na--, 2- or
4-[.sup.+ NH.sub.3 Cl.sup.- ]--, 3,4,5-trimethylphen-1-yl,
2,4,6-trimethylphen-1-yl, 4-trifluoromethyl-phenyl or
3,5-di(trifluoro-methyl)phenyl.
6. A compound of formula III according to claim 1, wherein R.sub.10 and
R.sub.11 are cyclohexyl, tert-butyl, phenyl, 2- or 4-methylphen-1-yl, 2-
or 4-methoxyphen-1-yl, 2- or 4-(dimethyl-amino)phen-1-yl,
3,5-dimethyl-4-(dimethylamino)phen-1-yl or
3,5-dimethyl-4-methoxyphen-1-yl.
7. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 are C.sub.1 -C.sub.8 alkyl.
8. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 are identical and are isopropyl or tert-butyl.
9. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 as cycloalkyl contain from 5 to 8 carbon atoms.
10. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 are unsubstituted phenyl or phenyl substituted by 1 or 2
substituents.
11. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 as substituted phenyl are 2-methyl-, 3-methyl-, 4-methyl-, 2- or
4-ethyl-, 2- or 4-isopropyl-, 2- or 4-tert-butyl-, 2-methoxy-, 3-methoxy-,
4-methoxy-, 2- or 4-ethoxy-, 4-trimethylsilyl-, 2- or 4-fluoro-,
2,4-difluoro-, 2- or 4-chloro-, 2,4-dichloro-, 2,4-dimethyl-,
3,5-dimethyl-, 2-methoxy-4-methyl-, 3,5-dimethyl-4-methoxy-,
3,5-dimethyl-4-(dimethylamino)-, 2- or 4-amino-, 2- or 4-methylamino-, 2-
or 4-(dimethylamino)-, 2- or 4-SO.sub.3 H--, 2- or 4-SO.sub.3 Na--, 2- or
4-[.sup.+ NH.sub.3 Cl.sup.- ]--, 3,4,5-trimethylphen-1-yl,
2,4,6-trimethylphen-1-yl, 4-trifluoromethyl-phenyl or
3,5-di(trifluoro-methyl)phenyl.
12. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 are identical and are phenyl, cyclohexyl, 2- or
4-methylphen-1-yl, 2- or 4-methoxyphen-1-yl, 2- or
4-(dimethyl-amino)phen-1-yl, 3,5-dimethyl-4-(dimethylamino)phen-1-yl or
3,5dimethyl-4-methoxyphen-1-yl.
13. A compound of formula VI according to claim 1, wherein R.sub.12 and
R.sub.13 are identical radicals and are cyclohexyl or phenyl.
14. A compound of formula I according to claim 1, wherein R.sub.1 is methyl
and R.sub.12 and R.sub.13 are each cyclohexyl or phenyl and R.sub.10 and
R.sub.11 are phenyl, cyclohexyl or tert-butyl.
15. A process for the preparation of a compound of formula VI, wherein a
compound of formula III according to claim 1 reacted with a compound of
formula H--P(R.sub.12 R.sub.13) in acetic acid, with R.sub.12 and R.sub.13
being as defined in claim 1.
16. A compound of formula VI
##STR32##
R.sub.1 is C.sub.1 -C.sub.8 alkyl, phenyl or phenyl substituted by from 1
to 3 C.sub.1 -C.sub.4 alkoxy substituents;
R.sub.10 and R.sub.11 are identical or different and are C.sub.1 -C.sub.12
alkyl, C.sub.5 -C.sub.12 cycloalkyl, phenyl, C.sub.5 -C.sub.12 cycloalkyl
substituted by C.sub.1 -C.sub.4 alkyl or by C.sub.1 -C.sub.4 alkoxy, or
phenyl substituted by from one to three C.sub.1 -C.sub.4 alkyl, C.sub.1
-C.sub.4 alkoxy, --SiR.sub.4 R.sub.5 R.sub.6, halogen, --SO.sub.3 M,
--CO.sub.2 M, --PO.sub.3 M,--NR.sub.7 R.sub.8, --(.sup.+ NR.sub.7 R.sub.8
R.sub.9)X.sup.- or C.sub.1 -C.sub.5 fluoroalkyl substituents;
Hal is F, Cl, Br or I; and
R.sub.12 and R.sub.13 are each independently of the other C.sub.1 -C.sub.12
alkyl, C.sub.5 -C.sub.12 cycloalkyl, phenyl, C.sub.5 -C.sub.12 cycloalkyl
substituted by C.sub.1 -C.sub.4 alkyl or by C.sub.1 -C.sub.4 alkoxy, or
phenyl mono- or poly-substituted by from one to three C.sub.1 -C.sub.4
alkyl, C.sub.1 -C.sub.4 alkoxy, --SiR.sub.4 R.sub.5 R.sub.6, halogen,
--SO.sub.3 M, --CO.sub.2 M, --PO.sub.3 M, --NR.sub.7 R.sub.8, --(.sup.+
NR.sub.7 R.sub.8 R.sub.9)X.sup.- or C.sub.1 -C.sub.5 fluoroalkyl
substituents; or the group --PR.sub.12 R.sub.13 is a radical of formula
IV, IVa, IVb or IVc
##STR33##
R.sub.4, R.sub.5 and R.sub.6 are each independently of the others C.sub.1
-C.sub.12 alkyl or phenyl;
R.sub.7 and R.sub.8 are H, C.sub.1 -C.sub.12 alkyl or phenyl or R.sub.7 and
R.sub.8 together are tetramethylene, pentamethylene or
3-oxa-1,5-pentylene;
R.sub.9 is H or C.sub.1 -C.sub.4 alkyl;
M is H or an alkali metal;
X.sup.- is the anion of a monobasic acid.
17. A process for the catalytic hydrogenation of carbon/carbon or
carbon/hetero atom double bonds wherein the process comprises contacting a
compound containing the double bonds over a rhodium or iridium ligand of
formula III.
18. A process for the catalytic hydrogenation of carbon/carbon or
carbon/hetero atom double bonds wherein the process comprises contacting a
compound containing the double bonds over a rhodium or iridium ligand of
formula VI.
19. An inorganically or polymerically bonded rhodium or iridium ligand of
formula VI.
Description
The invention relates to ferrocenes substituted in the 1,2- and
1'-positions and to processes for the preparation thereof.
Ferrocenyldiphosphine ligands having a silylene group are important
intermediates for ferrocenyldiphosphines, and their metal complexes with
transition metals such as rhodium or iridium, bonded via that silylene
group to inorganic or polymeric organic carriers. Those complexes are used
widely in the hydrogenation of organic double or triple bonds, especially
olefinic double bonds and carbon-hetero atom double bonds. The complexes
are suitable especially for enantioselective hydrogenation using chiral
ferrocenyldiphosphines and corresponding prochiral unsaturated compounds.
EP-A-0-496 699 and EP-A-0 496 700 disclose silane-group-containing
dioxolan- and pyrrolidine-diphosphines and their rhodium or iridium
complexes that are fixed to an inorganic carrier such as, for example, a
silicate. In that manner there is obtained in the hydrogenation a
heterogeneous reaction mixture from which the inorganically fixed catalyst
can readily be separated when the reaction is complete.
W. R. Cullen et. al. describe in J. of Organometallic Chemistry, 333
(1987), 269-280 ferrocene derivatives, such as, for example,
N,N-dimethyl-1-(2-diphenylphosphino-ferrocenyl)ethylamine that is bonded
directly to an oxidised polystyrene group. In the procedure proposed
therein a maximum of 20% of the ferrocene derivative used is bonded to the
polymeric carrier and the ferrocenyl ligand is bonded to the polymer
non-specifically and non-selectively partly via one or the other
cyclopentadienyl ring. As a result of the direct bonding to the polymer
skeleton the mobility of the phosphine ligand is likewise restricted.
It appears desirable to start from starting materials having known
properties and to modifiy those starting materials using catalytically
active compounds in such a manner that the properties are altered only
very slightly and there are no inclusions or any other alterations to the
catalytically active part; depending on the hydrogenation reaction, either
inorganically or organically bonded ferrocenyldiphosphine ligands may be
more advantageous.
However, it is also possible further to functionalise those silylated
ferrocenyldiphosphines in such a manner that they are copolymerisable, for
example, via an olefinically unsaturated bond. Such procedures are
described, for example, in J. Org. Chem. 1981, 46, 2960-2965.
In the case of polymer-bonded ferrocenyldiphosphine ligands, for example,
the reaction to be catalysed can be carried out heterogeneously or
homogeneously depending upon the polymer chosen. The polymer may be so
selected and also subsequently so modified in a targeted manner that the
catalyst can readily be separated off and re-used after the reaction. The
catalysts may be re-used several times. By the choice of the polymer it is
possible to match the catalyst in an optimum manner to the reaction medium
during the hydrogenation step and then to remove it completely afterwards,
which is of particular importance in relation to hydrogenation carried out
on an industrial scale.
In all cases the recovery of the noble metals present is facilitated if the
catalyst has to be changed after frequent recycling. It is often also
possible to dispense with further purification of the hydrogenated product
since the catalyst can generally be removed quantitatively.
Ferrocenyldiphosphines that contain an organic radical bonded via a
silylene group to a cyclopentadienyl ring can be immobilised in a simple
manner both on inorganic and on polymeric organic carriers or, after the
introduction of a polymerisable group, can be immobilised also by
copolymerisation. With rhodium and iridium the immobilised
ferrocenyldiphosphine ligands form complexes that can be used as highly
active catalysts in the enantioselective hydrogenation of carbon-carbon,
carbon-nitrogen or carbon-oxygen double bonds. The selectivity and the
total yield are surprisingly high for immobilised systems. The iridium
catalysts are especially well suited to imine hydrogenation since they
have clearly the highest activity and the highest catalyst productivity in
comparison with other immobilised systems. Their selectivity is likewise
very good. The catalysts can readily be separated from the reaction
solution and used again. There are virtually no losses of metal and
ligand. The use of those immobilised catalysts therefore enables
hydrogenation to be carried out economically, especially on an industrial
scale.
The preparation of such immobilised ferrocenyldiphosphines has been made
possible only by the provision of correspondingly functionalised
ferrocenyldiphosphines. Those intermediates and the preparation thereof
are therefore of great importance.
Ferrocenes that are substituted by two phosphine groups at a
cyclopentadienyl ring are known, and their preparation and use as ligands
in metal complexes for stereoselective hydrogenation is described, for
example, in EP-A-564 406.
No process has been disclosed hitherto that allows, for example
stereoselectively in (R)- or (S)-N,N-dimethyl-1-ferrocenylethylamine, in a
first step the introduction of a phosphorus group as an electrophile with
high selectivity at an already substituted cyclopentadienyl ring and in a
second step the introduction of a silylene group selectively at the other
cyclopentadienyl ring. Using that procedure, however, it is possible for
the first time to prepare a number of valuable intermediates for
ferrocenyldiphosphines and their metal complexes.
Dihalogenated, but otherwise unsubstituted, ferrocenes having a halogen
atom bonded to both cyclopentadienyl groups in the 1- and 1'-positions are
known, for example, from R. F. Kovar et al., Organometal. Chem. Syn., 1
(1970/1971) 173-181. Their preparation by means of lithiation and
subsequent halogenation is likewise diclosed therein.
However, 1,1'-dihalogenated ferrocenes substituted in the 2-position have
not been disclosed hitherto.
The invention accordingly relates to compounds of formula I
##STR4##
R.sub.1 is C.sub.1 -C.sub.8 alkyl, phenyl or phenyl substituted by from 1
to 3 C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy substituents;
R.sub.2 and R.sub.3 are each independently of the other hydrogen or C.sub.1
-C.sub.12 alkyl; and
Hal is F, Cl, Br or 1.
R.sub.1 as alkyl is preferably linear. It preferably contains from 1 to 4
carbon atoms. Examples of such alkyl are methyl, ethyl, n- and iso-propyl,
n-, iso- and tert-butyl, pentyl, hexyl, heptyl and octyl. Preference is
given to methyl and ethyl, and methyl is especially preferred.
R.sub.1 as substituted phenyl preferably contains 1 or 2 substituents.
Alkyl substituents may be, for example, methyl, ethyl, n- and iso-propyl,
n-, iso- and tert-butyl; methyl and ethyl are preferred. Alkoxy
substituents may be, for example, methoxy, ethoxy, n- and iso-propoxy,
n-iso- and tert-butoxy; methoxy and ethoxy are preferred. In a group of
compounds of formula I, R.sub.1 is preferably phenyl or phenyl substituted
by 1 or 2 C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy substituents.
R.sub.2 and R.sub.3 as alkyl may be linear or branched. Examples of C.sub.1
- to C.sub.8 -alkyl are mentioned above and include in addition the
various isomers of nonyl, decyl, undecyl and dodecyl. R.sub.2 and R.sub.3
may also be bonded to one another and form a cyclic alkyl group. Resulting
examples are pyrrolidine and piperidine.
Preferably R.sub.2 and R.sub.3 are each independently of the other
hydrogen, methyl or ethyl, and are especially both hydrogen or methyl.
Hal is preferably Cl, Br or I.
The compounds of formula I can be prepared in accordance with analogous
processes in a manner known per se, as described, for example, by R. F.
Kovar et al., Organometal. Chem. Syn., 1 (1970/1971) 173-181 for the
reaction of di-lithiated compounds with halogenating agents or by T.
Hayashi et al., Bull Chem. Soc. Jpn., 53 (1980) 1138-1151 for
stereo-selective lithiation.
The invention relates also to a process for the preparation of compounds of
formula I wherein a compound of formula II
##STR5##
R.sub.1, R.sub.2 and R.sub.3 are as defined above, is reacted in an inert
organic solvent first with an equivalent of alkyllithium and then, in the
presence of an amine complexing agent for Li, with a second equivalent of
alkyllithium and the product is then reacted with a halogenating agent.
An example of an amine complexing agent for Li is
N,N,N,N-tetramethylethylenediamine. Alkyllithium is to be understood in
the context of this invention as being preferably tert-butyl-, sec-butyl-
or n-butyl-lithium.
Halogenating agents are known in the general prior art for many reactions.
Some are also mentioned, for example, in Gmelin, Handbuch der
Anorganischen Chemie, Eisen-Organische Verbindungen Teil A Ferrocen 7,
Eighth Edition, Springer Verlag 1980, pages 128-136.
Preference is given to a halogenating agent selected from the group
consisting of Cl.sub.2, hexa-chloroethane, 1,2-dichlorotetrafluoroethane,
toluene-4-sulfonyl chloride, Br.sub.2, 1,2-dibromo-tetrachloroethane,
1,2-dibromotetrafluoroethane, toluene-4-sulfonyl bromide,
2,3-dimethyl-2,3-dibromobutane, I.sub.2, 1,2-diiodotetrafluoroethane,
perfluoropropyl iodide, perfluoroethyl iodide, toluene-4-sulfonyl iodide
and perfluoromethyl iodide.
The compounds of formula I act as starting materials for the preparation of
compounds of formula III which are likewise novel and a subject of this
invention.
The invention relates also to compounds of formula III
##STR6##
R.sub.1, R.sub.2, R.sub.3 and Hal are as defined above,
R.sub.10 and R.sub.11 are identical or different and are C.sub.1 -C.sub.12
alkyl, C.sub.5 -C.sub.12 cycloalkyl, phenyl, C.sub.5 -C.sub.12 cycloalkyl
substituted by C.sub.1 -C.sub.4 alkyl or by C.sub.1 -C.sub.4 alkoxy, or
phenyl substituted by from one to three C.sub.1 -C.sub.4 alkyl, C.sub.1
-C.sub.4 alkoxy, --SiR.sub.4 R.sub.5 R.sub.6, halogen, --SO.sub.3 M,
--CO.sub.2 M, --PO.sub.3 M, --NR.sub.7 R.sub.8, --[.sup.+ NR.sub.7 R.sub.8
R.sub.9 ]X.sup.- or C.sub.1 -C.sub.5 fluoroalkyl substituents; or
the group --PR.sub.10 R.sub.11 is a radical of formula IV, IVa, IVb or IVc
##STR7##
R.sub.4, R.sub.5 and R.sub.6 are each independently of the others C.sub.1
-C.sub.12 alkyl or phenyl;
R.sub.7 and R.sub.8 are H, C.sub.1 -C.sub.12 alkyl or phenyl or R.sub.7 and
R.sub.8 together are tetramethylene, pentamethylene or
3-oxa-1,5-pentylene;
R.sub.9 is H or C.sub.1 -C.sub.4 alkyl;
M is H or an alkali metal;
X.sup.- is the anion of a monobasic acid.
R.sub.10 and R.sub.11 as alkyl may be linear or branched and they contain
preferably from 1 to 8 and especially from 1 to 4 carbon atoms. Examples
of such alkyl are methyl, ethyl, n- and iso-propyl, n-, iso- and
tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and
dodecyl. Methyl, ethyl, n- and iso-propyl, n-, iso- and tert-butyl are
preferred. When R.sub.10 and R.sub.11 are identical, as alkyl they are
especially isopropyl or tert-butyl.
R.sub.10 and R.sub.11 as cycloalkyl contain preferably from 5 to 8 and
especially 5 or 6 ring carbon atoms. Examples of cycloalkyl are
cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl and
cyclododecyl. Preference is given to cyclopentyl and cyclohexyl, and
cyclohexyl is especially preferred.
The cycloalkyl may be substituted, for example by from 1 to 3 alkyl or
alkoxy substituents. Examples of such substituents have been given above.
Methyl and ethyl and methoxy and ethoxy are preferred. Examples of
substituted cycloalkyl are methyl- and methoxy-cyclopentyl and
-cyclohexyl.
R.sub.10 and R.sub.11 as substituted phenyl preferably contain 1 or 2
substituents. When phenyl contains 2 or 3 substituents, those substituents
may be identical or different.
Examples of alkyl and alkoxy substituents have been given above; preferred
alkyl and alkoxy substituents for phenyl are methyl, ethyl and methoxy and
ethoxy.
When the phenyl substituent is halogen, it is preferably --F, --Cl or --Br.
When the phenyl substituent is C.sub.1 -C.sub.5 fluoroalkyl, it is fully or
partially fluorinated C.sub.1 -C.sub.5 alkyl. Examples thereof are the
position isomers of mono- to deca-fluoropentyl, mono- to octa-fluorobutyl,
mono- to hexa-fluoropropyl, mono- to tetra-fluoroethyl and mono- and
di-fluoromethyl. Of the partially fluorinated alkyl radicals, those of the
formulae --CF.sub.2 H and --CF.sub.2 (C.sub.1 -C.sub.4 alkyl) are
especially preferred. Special preference is given to perfluorinated alkyl.
Examples thereof are perfluoropentyl, perfluorobutyl, perfluoropropyl,
perfluoroethyl and especially trifluoromethyl. The fluorine-substituted
alkyl groups are preferably bonded in the 3-, 4- and 5-positions.
R.sub.4, R.sub.5 and R.sub.6 may be linear or branched alkyl that contains
preferably from 1 to 8 and especially from 1 to 4 carbon atoms. Examples
of alkyl have been given above. Preferred alkyl is methyl, ethyl,
n-propyl, n-butyl or tert-butyl. The substituent --SiR.sub.4 R.sub.5
R.sub.6 is preferably tri-methylsilyl.
Of the acid phenyl substituents --SO.sub.3 M, --CO.sub.2 M and --PO.sub.3
M, the groups --SO.sub.3 M and --CO.sub.2 M are preferred. M is preferably
H, Li, Na or K.
R.sub.7 and R.sub.8 as alkyl contain preferably from 1 to 6 and especially
from 1 to 4 carbon atoms. The alkyl is preferably linear. Preferred
examples are methyl, ethyl, n-propyl and n-butyl. R.sub.9 as alkyl is
preferably methyl.
X.sup.- as an anion of a monobasic acid is preferably Cl.sup.-, Br.sup.-
or the anion of a carboxylic acid, for example formate, acetate,
trichloroacetate or trifluoroacetate.
Preferred examples of R.sub.10 and R.sub.11 as substituted phenyl are
2-methyl-, 3-methyl-, 4-methyl, 2- or 4-ethyl-, 2- or 4-isopropyl-, 2- or
4-tert-butyl-, 2-methoxy-, 3-methoxy-, 4-methoxy-, 2- or 4-ethoxy-,
4-trimethylsilyl-, 2- or 4-fluoro-, 2,4-difluoro-, 2- or 4-chloro-,
2,4-dichloro-, 2,4-dimethyl-, 3,5-dimethyl-, 2-methoxy-4-methyl-,
3,5-dimethyl-4-methoxy-, 3,5-dimethyl-4-(dimethylamino)-, 2- or 4-amino-,
2- or 4-methylamino-, 2- or 4-(dimethylamino)-, 2- or 4-SO.sub.3 H--, 2-
or 4-SO.sub.3 Na--, 2- or 4-[.sup.+ NH.sub.3 Cl.sup.- ]--,
3,4,5-trimethylphen-1-yl, 2,4,6-trimethylphen-1-yl,
4-trifluoromethyl-phenyl or 3,5-di(trifluoromethyl)phenyl.
R.sub.10 and R.sub.11 are especially preferably cyclohexyl, tert-butyl,
phenyl, 2- or 4-methylphen-1-yl, 2- or 4-methoxyphen-1-yl, 2- or
4-(dimethylamino)phen-1-yl, 3,5-dimethyl-4-(dimethylamino)-phen-1-yl or
3,5-dimethyl-4-methoxyphen-1-yl, but especially cyclohexyl, phenyl,
4-methylphen-1-yl or tert-butyl.
The process for the preparation of compounds of formula III is likewise
novel and a subject of this invention.
The process for the preparation of compounds of formula III is as follows:
in a first step alkyllithium is added to a compound of formula I in an
inert organic solvent and allowed to react and then an organic solution of
a compound of formula V CIP(R.sub.10 R.sub.11) (V) is added and reacted
further to form a compound of formula III wherein R.sub.10 and R.sub.11
have the definitions and preferred meanings given above.
The substitution of the halogen atom takes place predominantly at the
cyclopentadienyl ring that carries the second substituent (alkylamine). It
is therefore possible using this process to obtain asymmetric ferrocenes
in a good yield, which is of great significance with regard to commercial
production.
The process is preferably carried out by adding alkyllithium at a
temperature of from -90 to +20.degree. C.
In the second step, the compound of formula V is added preferably at a
temperature of from -90 to +20.degree. C.
The invention relates also to ferrocenyldiphosphines of formula VI that are
obtained using compounds of formula III as starting materials,
##STR8##
R.sub.1, R.sub.10, R.sub.11 and Hal have the definitions and preferred
meanings given above, and R.sub.12 and R.sub.13 are each independently of
the other C.sub.1 -C.sub.12 alkyl, C.sub.5 -C.sub.12 cycloalkyl, phenyl,
C.sub.5 -C.sub.12 cyclo-alkyl substituted by C.sub.1 -C.sub.4 alkyl or by
C.sub.1 -C.sub.4 alkoxy, or phenyl mono- or poly-substituted by from one
to three C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --SiR.sub.4
R.sub.5 R.sub.6, halogen, --SO.sub.3 M, --CO.sub.2 M, --PO.sub.3 M,
--NR.sub.7 R.sub.8, --[.sup.+ NR.sub.7 R.sub.8 R.sub.9 ]X.sup.- or
C.sub.1 -C.sub.5 fluoroalkyl substituents; or the group --PR.sub.12
R.sub.13 is a radical of formula IV, IVa, IVb or IVc
##STR9##
R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, M and X.sup.- have
the definitions and preferred meanings given above.
Examples of alkyl, cycloalkyl, substituted phenyl and fluoroalkyl have
already been given above and apply also to the definitions of R.sub.12 and
R.sub.13.
R.sub.12 and R.sub.13 are preferably C.sub.1 -C.sub.8 alkyl. Examples of
C.sub.1 -C.sub.8 alkyl have already been mentioned.
R.sub.12 and R.sub.13 preferably are identical and are isopropyl or
tert-butyl.
R.sub.12 and R.sub.13 as cycloalkyl preferably contain from 5 to 8 carbon
atoms.
Another preferred group of compounds is obtained when R.sub.12 and R.sub.13
are unsubstituted phenyl or phenyl substituted by 1 or 2 substituents.
R.sub.12 and R.sub.13 as substituted phenyl are especially preferably
2-methyl-, 3-methyl-, 4-methyl-, 2- or 4-ethyl-, 2- or 4-isopropyl-, 2- or
4-tert-butyl-, 2-methoxy-, 3-methoxy-, 4-methoxy-, 2- or 4-ethoxy-,
4-trimethylsilyl-, 2- or 4-fluoro-, 2,4-difluoro-, 2- or 4-chloro-,
2,4-dichloro-, 2,4-dimethyl-, 3,5-dimethyl-, 2-methoxy-4-methyl-,
3,5-dimethyl-4-methoxy-, 3,5-dimethyl-4-(dimethylamino)-, 2- or 4-amino-,
2- or 4-methylamino-, 2- or 4-(dimethylamino)-, 2- or 4-SO.sub.3 H--, 2-
or 4-SO.sub.3 Na--, 2- or 4-[.sup.+ NH.sub.3 Cl.sup.- ]-,
3,4,5-trimethylphen-1-yl, 2,4,6-trimethylphen-1-yl,
4-trifluoromethyl-phenyl or 3,5-di(trifluoromethyl)phenyl.
A further group of especially preferred compounds is obtained when R.sub.12
and R.sub.13 are identical and are phenyl, cyclohexyl, 2- or
4-methylphen-1-yl, 2- or 4-methoxyphen-1-yl, 2- or
4-(dimethylamino)phen-1-yl, 3,5-dimethyl-4-(dimethylamino)phen-1-yl or
3,5-dimethyl-4-methoxyphen-1-yl; R.sub.12 and R.sub.13 are more especially
identical radicals and are cyclohexyl or phenyl.
Compounds wherein R.sub.1 is methyl, R.sub.12 and R.sub.13 are each
cyclohexyl or phenyl and R.sub.10 and R.sub.11 are phenyl, cyclohexyl or
tert-butyl are especially preferred.
The process for the preparation of compounds of formula VI can be carried
out analogously to processes known in the prior art. For example, that
substitution is disclosed in EP-A-612 758.
The process for the preparation of compounds of formula VI comprises
reacting a compound of formula III with a compound of formula
H--P(R.sub.12 R.sub.13) in acetic acid, with R.sub.12 and R.sub.13 having
the definitions and preferred meanings given above.
The compounds of formulae I, III and VI may be obtained in the form of
racemates, pure enantiomers or mixtures of enantiomers. If the synthesis
is carried out using enantiomerically pure compounds of formula II as
starting materials, there is formed very preferentially only one of the
two possible diastereoisomers of the compounds of formula I and
consequently also of the compounds of formula III and VI.
If racemates or optically active mixtures are used as starting materials,
they can be separated into the stereoisomers by means of known methods,
with chromatographic methods generally being preferred. The optical
isomers of compounds of formula VI especially are valuable starting
materials for the preparation of immobilised hydrogenation catalysts.
The isolation and purification of the compounds is carried out in
accordance with methods known per se, for example distillation,
extraction, crystallisation and/or chromatographic methods.
The compounds of formula VI can in a first step be lithiated with
alkyllithium in known manner, as described, for example, in J. Chem. Soc.
Chem. Commun., 1994, 2347-2348. In a further step, a compound of formula
VII ClSi(R.sub.14).sub.2 --(R.sub.15)--Cl (VII) is then added and reacted
to form compounds of formula VIII,
##STR10##
wherein the radicals R.sub.14 are each independently of the other C.sub.1
-C.sub.12 alkyl, C.sub.3 -C.sub.7 cycloalkyl, benzyl or phenyl or are
together C.sub.4 -C.sub.12 alkylene and R.sub.15 is C.sub.1 -C.sub.12
alkylene or phenylene. Preferably R.sub.14 is methyl and R.sub.15 is
propyl. R.sub.1 to R.sub.13 have been defined above.
The compounds of formula VIII can also be obtained by in a first step
lithiating compounds of formula III in accordance with known procedures
and then in a second step reacting with compounds of formula VII to form
compounds of formula IX
##STR11##
the definitions and preferred meanings of the radicals R.sub.1 to R.sub.15
have been given above.
The compounds of formula IX can be reacted further with a compound of
formula H--P(R.sub.12 R.sub.13) in acetic acid analogously to procedures
known in the prior art and, in this way too, compounds of formula VIII are
obtained. That substitution is disclosed by analogy in EP-A-612 758.
Compounds of formula IX may also be used as hydrogenation and
hydrosilylation catalysts analogously to the amine-group-containing
diphosphines described by Cullen et al. in Can. J. Chem. Vol. 60, 1982,
pages 1793 to 1799.
The compounds of formula IX can likewise be immobilised on polymers and
used as immobilised ligands in enantioselective catalytic reactions.
The compounds of formula VIII can be reacted further, in accordance with
known procedures, with compounds of formula X NH.sub.2 (C.sub.1 -C.sub.12
alkyl) (X) to form compounds of formula VIIIa
##STR12##
or the compounds of formula VIII are reacted first with potassium
phthalimide and then with hydrazine to form compounds of formula VIIIb
##STR13##
and, optionally, in a further step compounds of formula VIIIa or VIIIb can
be reacted with compounds of formula XI R.sub.a (R.sub.17 O).sub.2
Si--R.sub.16 --NCO (XI) to form compounds of formula VIIIc
##STR14##
wherein R.sub.a is C.sub.1 -C.sub.4 alkyl or OR.sub.17, A is NH or
N(C.sub.1 -C.sub.12 alkyl, R.sub.16 is C.sub.1 -C.sub.12 alkylene and
R.sub.17 is C.sub.1 -C.sub.12 alkyl.
The remaining radicals R.sub.1 to R.sub.15 have the definitions given
above, including the preferred meanings.
The reaction steps are analogy processes that are described, for example,
in EP-A-612 758 and in EP-A496 699. The step of amination to form the
compounds of formula VIIIa is known to the person skilled in the art from
current reference books on organic chemistry.
The compounds VIIIa and VIIIb can then be reacted to form a polymeric
organic material having structural repeating units of formula XII
##STR15##
A and R.sub.1 to R.sub.15 are as defined above, Q is a bridge group formed
by a diisocyanate, and PM is the radical of a polymer-forming monomer that
contains as functional group, bonded directly or in a side chain, a
hydroxy group or a primary or secondary amine group which is bonded to the
diphosphine via a bridge group Q formed by a diisocyanate.
Preferred diisocyanates are 1,6-bis[isocyanato]hexane,
5-isocyanato-3-(isocyanatomethyl)-1,1,3-trimethylcyclohexane,
1,3-bis[5-isocyanato-1,3,3-trimethyl-phenyl]-2,4-dioxo-1,3-diazetidine,
3,6-bis[9-isocyanato-nonyl]-4,5-di(1-heptenyl)cyclohexene,
bis[4-isocyanato-cyclohexyl]methane, trans-1,4-bis[isocyanato]cyclohexane,
1,3-bis[isocyanatomethyl]-benzene,
1,3-bis[1-isocyanato-1-methyl-ethyl]benzene,
1,4-bis[2-isocyanato-ethyl]cyclohexane,
1,3-bis[isocyanatomethyl]cyclohexane,
1,4-bis[1-isocyanato-1-methylethyl]-benzene,
bis[isocyanato]isododecylbenzene,1,4-bis[isocyanato]benzene,
2,4-bis[isocyanato]toluene, 2,6-bis[isocyanato]toluene,
2,4-/2,6-bis[isocyanato]toluene,
2-ethyl-1,2,3-tris[3-isocyanato-4-methyl-anilinocarbonyloxy]propane,
N,N'-bis[3-isocyanato-4-methyl-phenyl]urea,
1,4-bis[3-isocyanato-4-methylphenyl]-2,4-dioxo-1,3-diazetidine,
1,3,5-tris[3-isocyanato-4-methylphenyl]-2,4,6-trioxohexahydro-1,3,5-triazi
ne, 1,3-bis[3-isocyanato-4-methylphenyl]-2,4,5-trioxoimidazolidine,
bis[2-isocyanatophenyl]methane,
(2-isocyanatophenyl)-(4-isocyanato-phenyl)-methane,
bis[4-isocyanato-phenyl]methane,
2,4-bis[4-isocyanatobenzyl]-1-isocyanatobenzene,
[4-isocyanato-3-(4-isocyanato-benzyl)-phenyl]-[2-isocyanato-5-(4-isocyanat
o-benzyl)-phenyl]methane, tris[4-isocyanato-phenyl]methane,
1,5-bis[isocyanato]naphthalene and
4,4'-bis[isocyanato]-3,3'-dimethyl-biphenyl.
Especially preferred diisocyanates are 1,6-bis[isocyanato]hexane,
5-isocyanato-3-(isocyanatomethyl)-1,1,3-trimethylcyclohexane,
2,4-bis[isocyanato]toluene, 2,6-bis[isocyanato]-toluene,
2,4-/2,6-bis[isocyanato]toluene and bis[4-isocyanato-phenyl]methane.
The polymers according to the invention may be uncrosslinked thermoplastic,
crosslinkecd or structurally crosslinked polymers.
The polymers can be either polymerisates of olefinically unsaturated
monomers, for example polyolefins, polyacrylates, polyisoprenes,
polybutadiene, polystyrene, polyphenylene, polyvinyl chloride,
polyvinylidene chloride or polyallyl compounds. They may also be
polyaddition compounds, for example polyurethanes or polyethers.
Polycondensed products which may be mentioned are polyesters or polyamides
Preference is given to polymer-forming monomers selected from the group
consisting of styrene, p-methylstyrene and .alpha.-methylstyrene, at least
one of which contains a hydroxy group or a primary or secondary amine
group bonded as functional group.
Another preferred group of polymers is formed by monomers derived from
.alpha.,.beta.-unsaturated acids and their esters and amides, the
structural units of which contain a hydroxy group or a primary or
secondary amine group bonded as functional group.
Special preference is given to the monomers from the group of the acrylates
and the C.sub.1 -C.sub.4 alkyl esters thereof, methacrylates and the
C.sub.1 -C.sub.4 alkyl esters thereof, acrylamide and acrylonitrile, the
structural units of which contain a hydroxy group or a primary or
secondary amine group bonded as functional group in the ester or amide
group.
Preferably, the hydroxy-functional or primary or secondary amine-functional
monomers form from 1 to 100 mole %, preferably from 5 to 100 mole % and
especially from 10 to 100 mole %, of the polymer structure in the case of
soluble or swellable polymers in which the functional group is already
present.
In the case of crosslinked polymers, that are functionalised subsequently,
preferably from 1 to 50 mole %, especially from 1 to 20 mole %,
hydroxy-functional or primary or secondary amine-functional groups are
present, the molar percentages being based on the monomer forming the
majority of the polymer.
The loading of the polymer with ferrocenyldiphosphines according to the
invention is preferably from 5 to 100 mole %, especially from 5 to 50 mole
%, based on the available hydroxy group or primary or secondary amine
group of the polymer.
The polymeric carriers can be prepared as follows: polymers having
structural repeating units of at least one monomer that contains a hydroxy
group or a primary or secondary amine group bonded as functional group
directly in the polymer spine or in a side chain A) in a first step are
fully or partially reacted, in an inert organic solvent, with a
diisocyanate that forms a bridge group Q and in a second step the product
is reacted with a diphosphine that contains tertiary phosphine groups
bonded in the 1,2-positions of one cyclopentadienyl ring, one of which
tertiary phosphine groups is bonded directly and the other of which is
bonded via a group CHR.sub.1 to the cyclopentadienyl ring, and that
contains a silylene group --Si(R.sub.14).sub.2 --R.sub.15 -A- bonded to
the other cyclopentadienyl radical; or B) in a first step a diphosphine
that contains tertiary phosphine groups bonded in the 1,2-positions of one
cyclopentadienyl ring, one of which tertiary phosphine groups is bonded
directly and the other of which is bonded via a group CHR.sub.1 to the
cyclopentadienyl ring, and that contains a silylene group
--Si(R.sub.14).sub.2 -R.sub.15 -A- bonded to the other cyclopentadienyl
ring is fully or partially reacted, in an inert organic solvent, with a
diisocyanate that forms a bridge group Q and in a second step the product
is fully or partially reacted with a polymer having structural repeating
units of at least one monomer that contains a hydroxy group or a primary
or secondary amine group bonded as functional group, and C) any free
isocyanate groups that remain are crosslinked with a C.sub.2 -C.sub.24
diol or C.sub.2 -C.sub.24 di-amine or removed by reaction with a C.sub.2
-C.sub.12 alcohol or C.sub.2 -C.sub.12 amine.
The diisocyanates forming a bridge group Q can be reacted with the amine or
hydroxy groups of the polymer and of the diphosphine at room temperature
or elevated temperature, for example from 30.degree. to 100.degree. C. in
accordance with methods known in the literature.
The subsequent introduction of, for example, a hydroxy group into highly
crosslinked poly-styrene can be carried out in accordance with known
procedures. First chloromethylation is carried out as described in J. Mol.
Catal. 51 (1989), 13-27 and then hydrolysis in accordance with the method
given by J. M. Frechet et al. in Polymer, 20 (1979) 675-680.
The compounds of formula VIIId can be reacted to form
ferrocenyldiphosphines fixed on inorganic carriers by means of an
analogous reaction procedure--as disclosed in EP-A-0 496 699.
The solid carrier T can be a silicate or a semi-metal oxide or metal oxide
or a glass, which are preferably present in the form of powders having
average particle diameters of from 10 nm to 2000 .mu.m, preferably from 10
nm to 1000 .mu.m and especially from 10 nm to 500 .mu.m.
They may be either compact or porous particles. Porous particles preferably
have large internal surface areas, for example from 1 to 1200 m.sup.2,
preferably from 30 to 600 m.sup.2. Examples of oxides and silicates are
SiO.sub.2, TiO.sub.2, ZrO.sub.2, MgO, NiO, WO.sub.3, Al.sub.2 O.sub.3,
La.sub.2 O.sub.3, silica gels, clays and zeolites. Preferred carriers are
silica gels, aluminium oxide, titanium oxide or glass and mixtures
thereof. An example of a glass as carrier is "controlled pore glass" which
is commercially available.
Using the organically or inorganically fixed diphosphines it is possible to
prepare metal complexes of rhodium or iridium by reacting the organic or
inorganic carriers to which the diphosphines are bonded with a metal
compound of the formula [Me(Y)D].sub.2 or Me(Y).sub.2.sup.+ E.sup.-
wherein Me is rhodium or iridium, Y represents two monoolefin ligands or
one diene ligand; D is --Cl, --Br or --I and E.sup.- is the anion of an
oxy acid or complex acid.
Metal complexes in which Y is 1,5-hexadiene, 1,5cyclooctadiene or
norbornadiene are preferred.
In the metal complexes according to the invention D is preferably --Cl,
--Br or --I.
In the preferred metal complexes, E.sup.- is ClO.sub.4.sup.-, CF.sub.3
SO.sub.3.sup.-, CH.sub.3 SO.sub.3.sup.-, HSO.sub.4.sup.-, BF.sub.4.sup.-,
B(phenyl).sub.4.sup.-, PF.sub.6.sup.-, SbCl.sub.6.sup.-, AsF.sub.6.sup.-
or SbF.sub.6.sup.-.
The reaction is advantageously carried out under an inert gas atmosphere,
for example argon, and expediently at temperatures of from 0 to 40.degree.
C., preferably at room temperature, in the case of soluble polymer-bonded
diphosphines. A solvent or mixture of solvents is advantageously co-used,
for example hydrocarbons (benzene, toluene, xylene), halogenated
hydrocarbons (methylene chloride, chloroform, carbon tetrachloride,
chlorobenzene), alkanols (methanol, ethanol, ethylene glycol monomethyl
ether), and ethers (diethyl ether, dibutyl ether, ethylene glycol dimethyl
ether) or mixtures thereof.
Preferably the metal complexes are used for the asymmetric hydrogenation of
prochiral compounds having carbon-carbon or carbon-hetero atom double
bonds, especially the Ir complexes for the hydrogenation of asymmetric
ketimines. Such hydrogenations with soluble homogeneous
ferrocenyldiphosphine metal complexes are disclosed, for example, in
EP-A-612 758.
The following Examples illustrate the invention.
General process procedure:
All operations are carried out under an inert gas atmosphere (argon or
nitrogen).
Abbreviations used:
TMEDA: N,N,N,N-tetramethylethylenediamine
n-BuLi: n-butyllithium
COD: 1,5-cyclooctadiene
EXAMPLE A1
Preparation of the Compound of Formula 1
(R)-N,N-Dimethyl-1-[(S)-1',2bis(chloro)ferrocenyl]ethylamine
##STR16##
2.92 ml (4.6 mmol) of a 1.6 M n-BuLi solution are added dropwise at room
temperature, with stirring, to a solution of 1 g (3.9 mmol) of
(R)-N,N-dimethyl-1-ferrocenylethylamine in 8 ml of diethyl ether. After
1.5 hours, a further solution consisting of 2.92 ml (4.6 mmol) of a 1.6 M
BuLi solution in hexane and 0.67 ml (4.4 mmol) of TMEDA is added dropwise
and the reaction mixture is stirred for 5 hours. The dark-brown, cloudy
reaction mixture is then cooled to -72 to -78.degree. C. with a dry
ice/isopropanol bath and, with stirring, 2.21 g (9.4 mmol) of
hexachloroethane are slowly added in portions in such a manner that the
temperature of the mixture does not exceed -74.degree. C. The mixture is
stirred for a further 1 hour with cooling and then for a further 2 hours
without cooling. 20 ml of ice-water are added to the resulting orange
suspension and the mixture is repeatedly extracted by shaking wth 5 ml of
ethyl acetate. The organic phases are collected, washed with water, dried
with Na.sub.2 SO.sub.4 and concentrated in a rotary evaporator. The brown
crude product is purified by chromatography (silica gel: Merck 60; eluant:
acetone). 0.54 g of compound 2 is obtained (yield 43%, orange oil).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.53 (d, 3H, J=7,
C--CH.sub.3), 2.13 (s, 6H, N(CH.sub.3).sub.2), 3.83 (q, 1H, J=7, CH--Me),
4.0-4.5 (m, 7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4).
Microanalysis, calculated for C.sub.14 H.sub.17 Cl.sub.2 FeN: C, 51.57; H,
5.26; N, 4.30; Cl, 21.75. found: C, 51.42; H, 5.28; N, 4.28; Cl, 21.48.
EXAMPLE A2
Preparation of the Compound of Formula 2
(R)-N,N-Dimethyl-1-[(S)-1',2bis(bromo)ferrocenyl]ethylamine
##STR17##
20.6 ml (33 mmol) of a 1.6 M n-BuLi solution are added dropwise at room
temperature, with stirring, to a solution of 7.71 g (30 mmol) of
(R)-N,N-dimethyl-1-ferrocenylethylamine in 50 ml of diethyl ether. After
1.5 hours, a further solution consisting of 22.5 ml (36 mmol) of a 1.6 M
BuLi solution in hexane and 4.95 ml (33 mmol) of TMEDA is added dropwise
and the reaction mixture is stirred overnight. The dark-brown, cloudy
reaction mixture is then cooled to -72 to -78.degree. C. in a dry
ice/isopropanol bath and, with stirring, 7.9 ml (66 mmol) of
1,2-di-bromotetrafluoroethane are slowly added dropwise in such a manner
that the temperature of the mixture does not exceed -74.degree. C. The
mixture is stirred for a further 1 hour with cooling and then for a
further 2 hours without cooling. 50 ml of ice-water are added to the
resulting orange suspension and the mixture is repeatedly extracted by
shaking wth 25 ml of ethyl acetate. The organic phases are collected,
washed with water, dried with Na.sub.2 SO.sub.4 and concentrated in a
rotary evaporator. The brown crude product is purified by chromatography
(silica gel: Merck 60; eluant: acetone). 7.5 g of compound 2 are obtained
(yield 60%, brown oil).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.53 (d, 3H, J=7,
C--CH.sub.3), 2.13 (s, 6H, N(CH.sub.3).sub.2), 3.78 (q, 1H, J=7, CH--Me),
4.03-4.5 (m, 7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4).
Microanalysis calculated for C.sub.14 H.sub.17 NBr.sub.2 Fe: C, 40.52; H,
4.13; N, 3.38; Br, 38.51; Fe, 13.46. found: :C, 40.80; H, 4.10; N, 3.30;
Br, 38.18.
EXAMPLE A3
Preparation of the Compound of Formula 3
(R)-N,N-Dimethyl-1-[(S)-1',2bis(iodo)ferrocenyl]ethylamine
##STR18##
2.92 ml (4.6 mmol) of a 1.6 M n-BuLi solution are added dropwise at room
temperature, with stirring, to a solution of 1 g (3.9 mmol) of
(R)-N,N-dimethyl-1-ferrocenylethylamine in 8 ml of diethyl ether. After
1.5 hours, a further solution consisting of 2.92 ml (4.6 mmol) of a 1.6 M
BuLi solution in hexane and 0.67 ml (4.4 mmol) of TMEDA is added dropwise
and the reaction mixture is stirred for 5 hours. The dark-brown, cloudy
reaction mixture is then cooled to -72 to -78.degree. C. in a dry
ice/isopropanol bath and, with stirring, 2.37 g (9.3 mmol) of iodine are
slowly added in portions in such a manner that the temperature of the
mixture does not exceed -74.degree. C. The mixture is stirred for a
further 1 hour with cooling and then for a further 2 hours without
cooling. 20 ml of ice-water are added to the resulting orange suspension
and the mixture is repeatedly extracted by shaking wth 20 ml of ethyl
acetate. The organic phases are collected, washed with water, dried with
Na.sub.2 SO.sub.4 and concentrated in a rotary evaporator. The brown crude
product is purified by chromatography (silica gel: Merck 60; eluant:
acetone). 0.17 g of compound 3 is obtained (yield 9%, reddish-brown oil).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.50 (d, 3H, J=7,
C--CH.sub.3), 2.15 (s, 6H, N(CH.sub.3).sub.2), 3.65 (q, 1H, J=7, CH--Me),
4.03-4.5 (m, 7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4).
Microanalysis calculated for C.sub.14 H.sub.17 NI.sub.2 Fe: C, 33.04; H,
3.37; N, 2.75; I, 49.87. found: C, 32.89; H, 3.56; N, 2.63; I, 49.08.
EXAMPLE A4
Preparation of the Compound of Formula 4
(R)-N,N-Dimethyl-1-[1'-(bromo),(S)-2-(diphenylphosphino)ferrocenyl]ethylami
ne
##STR19##
0.37 ml (0.6 mmol) of a 1.6 M BuLi solution in hexane is added dropwise at
-40 to -30.degree. C., with stirring, to a solution of 250 mg (0.6 mmol)
of the compound from Example 2 (compound 2) in 4 ml of diethyl ether. The
mixture is then cooled to -78.degree. C. and 0.133 ml (0.72 mmol) of
Cl--PPh.sub.2 is slowly added. The mixture is then allowed to rise slowly
to room temperature and is then stirred for a further 1 hour. 10 ml of
water are then added to the resulting yellow suspension and the mixture is
repeatedly extracted by shaking with ethyl acetate. The organic phases are
collected, washed with water, dried with Na.sub.2 SO.sub.4 and
concentrated in a rotary evaporator. The yellowish-brown crude product is
purified by chromatography over silica gel or Alox. 159 mg of compound 4
are obtained (yield 51%, orangeish-brown almost solid). If the same
reaction is carried out in pentane under conditions that are otherwise the
same, a yield of 61% is obtained.
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.25 (d, 3H, J=7,
C--CH.sub.3), 1.75 (s, 6H, N(CH.sub.3).sub.2), 4.15 (m, 1 H, J=7, CH--Me),
3.7-4.4 (m, 7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4), 7.1-7.65 (m, 10H,
P(C.sub.6 H.sub.5).sub.2. .sup.31 P--NMR (CDCl.sub.3): .delta. -24.568
EXAMPLE A5
Preparation of the Comoound of Formula 5
(R)-N,N-Dimethyl-1-[1'-(1"-dimethylsilyl-3"-chloropropyl)-(S)-2-diphenylpho
sphino-ferrocenyl]ethylamine
##STR20##
0.2 ml (0.32 mmol) of a 1.6 M BuLi solution in hexane is added dropwise at
-40 to -30.degree. C., with stirring, to a solution of 136 mg (0.26 mmol)
of compound 4 from Example 4 in 4 ml of diethyl ether. The mixture is then
cooled to -78.degree. C. and 0.056 ml (0.34 mmol) of
3-chloro-propyl-dimethylchlorosilane is slowly added. The mixture is then
allowed to rise slowly to room temperature and is then stirred for a
further 1 hour. 10 ml of water are then added to the resulting orange
suspension and the mixture is repeatedly extracted by shaking with ethyl
acetate. The organic phases are collected, washed with water, dried with
Na.sub.2 SO.sub.4 and concentrated in a rotary evaporator. The
yellowish-brown crude product is purified by chromatography (silica gel:
Merck 60; eluant: ethyl acetate). 85 mg of compound 5 are obtained (yield
50%, orange almost solid).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 0.05 (s, 3H,Si--CH.sub.3),
0.15 (s, 3H,Si--CH.sub.3), 0.61 (m, 2H, CH.sub.2 --Si), 1.28 (d, 3H, J=7,
C--CH.sub.3), 1.5-1.9 (m, 2H, CH.sub.2 --CH.sub.2 --Cl1.75), 1.78 (s, 6H,
N(CH.sub.3).sub.2), 3.4 (t, 3H, CH.sub.2 --Cl), 3.5-4.4, (m, 8H, C5H.sub.4
FeC.sub.5 H.sub.3 CH), 7.1-7.65 (m, 10H, P(C.sub.6 H.sub.5).sub.2. .sup.31
P--NMR (CDCl.sub.3): .delta. -23.306
EXAMPLE A6
Preparation of the Compound of Formula 6
(R)-1-[1'-(Bromo)-(S)-2-diphenylphosphino-ferrocenyl]ethyldicyclohexylphosp
hine
##STR21##
A mixture of 199 mg (0.38 mmol) of compound 4 from Example 4 and 0.093 ml
of dicyclo-hexylphosphine in 2 ml of acetic acid is stirred at 100.degree.
C. (bath temperature) for 2.5 hours. After cooling, 10 ml of water are
added to the orange solution and the mixture is repeatedly extracted by
shaking with toluene. The organic phases are collected, washed with water,
dried with Na.sub.2 SO.sub.4 and concentrated in a rotary evaporator. The
orange crude product is purified by chromatography (silica gel: Merck 60;
eluant: hexane/ethyl acetate 4/1). 174 mg of compound 6 are obtained
(yield 67%, orange almost solid).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 0.9-2 (m, 25H, P(C.sub.6
H.sub.11).sub.2, C--CH.sub.3), 3.25 (m, 1H, CH--CH.sub.3), 3.45-4.4 (m,
7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4), 7.1-7.7 (m, 10H, P(C.sub.6
H.sub.5).sub.2). .sup.31 P--NMR (CDCl.sub.3): .delta. -27.2 (d,
PPh.sub.2), 16.0 (d, Pcy.sub.2), JPP 35 Hz.
EXAMPLE A7
Preparation of the Compound of Formula 7
a)
(R)-1-[1'-(1"-Dimethylsilyl-3"-chloropropyl)-(S)-2-(diphenylphosphino)ferr
ocenyl]ethyl-dicyclohexylphosphine
##STR22##
0.36 g (1.8 mmol) of dicyclohexylphosphine in 2 ml of acetic acid is added
to 1 g (1.73 mmol) of compound 5 from Example 5 in 4 ml of acetic acid and
the mixture is stirred at 95.degree. C. in an oil bath for 90 minutes.
After cooling, the reddish-brown solution is extracted by shaking in 10 ml
of toluene and 30 ml of a 5% aqueous NaCl solution. The aqueous phase is
then extracted by shaking three times with 5 ml of toluene. The organic
phases are then collected, washed with 15 ml of water, dried with Na.sub.2
SO.sub.4 and concentrated in a rotary evaporator under reduced pressure.
The crude product is purified by column chromatography (eluant:
hexane/diethyl ether). 0.95 g of compound 7 is obtained (brown powder,
yield 75%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 15.8 (d, Pcy.sub.2), JPP 34 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 0.05 (s, 3H, Si--CH.sub.3), 0.15 (s, 3H, Si--CH.sub.3), 0.6 (m,
2H, CH.sub.2 --Si), 0.9-2.0 (m, 27H, cy, CH.sub.2 --CH.sub.2 --Cl,
CH--CH.sub.3), 3.41 (t, 2H, J=7, CH.sub.2 --Cl), 3.1-4.5 (m, 8H, C.sub.5
H.sub.4 FeC.sub.5 H.sub.3 CH), 7.1-7.75 (m, 10H, P(C.sub.6
H.sub.5).sub.2).
b)
(R)-1-[1'-(1"-Dimethylsilyl-3"-chloropropyl)-(S)-2-(diphenylphosphino)ferr
ocenyl]ethyl-dicyclohexylphosphine
0.2 ml (0.32 mmol) of a 1.6 M butyl-Li solution in hexane is added dropwise
at -40 to -30.degree. C., with stirring, to a solution of 167 mg (0.25
mmol) of compound 6 from Example 6 in 3 ml of diethyl ether. The mixture
is then cooled to -78.degree. C. and 0.057 ml (0.35 mmol) of
3-chloro-propyl-dimethylchlorosilane is slowly added. The mixture is then
allowed to rise slowly to room temperature and is then stirred for a
further 1 hour. 5 ml of water are then added to the resulting orange
suspension and the mixture is repeatedly extracted by shaking with
CH.sub.2 Cl.sub.2. The organic phases are collected, washed with water,
dried with Na.sub.2 SO.sub.4 and concentrated in a rotary evaporator. The
orange crude product is purified by chromatography (silica gel: Merck 60;
eluant: hexane/ethyl acetate 4/1). 127 mg of compound 7 are obtained
(yield 70%, orange almost solid).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 15.8 (d, Pcy.sub.2), JPP 34 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 0.05 (s, 3H, Si--CH.sub.3), 0.15 (s, 3H, Si--CH.sub.3), 0.6 (m,
2H, CH.sub.2 --Si), 0.9-2.0 (m, 27H, cy, CH.sub.2 --CH.sub.2 --Cl,
CH--CH.sub.3), 3.41 (t, 2H, J=7, CH.sub.2 --Cl), 3.1-4.5 (m, 8H, C.sub.5
H.sub.4 FeC.sub.5 H.sub.3 CH), 7.1-7.75 (m, 10H, P(C.sub.6
H.sub.5).sub.2).
EXAMPLE A8
Preparation of the Compound of Formula 8
The primary amine (8) is prepared by way of Gabriel synthesis (conversion
of the chloride into the phthalimide and freeing of the amine with
hydrazine hydrate) from compound (7) Example 7:
##STR23##
450 mg of potassium phthalimide and 120 mg of hexadecyltributylphosphonium
bromide (catalyst) are added to a solution of 1.4 g (1.94 mmol) of the
compound of formula 7 from Example 7 in 3 ml of DMF and the mixture is
stirred at 96.degree. C. for 1.5 hours. After cooling, the mixture is
extracted by shaking in water/toluene and the organic phase is dried with
sodium sulfate and concentrated in a rotary evaporator. After purification
by chromatography (eluant: hexane/ethyl acetate), 1.32 g of orange powder
are obtained (yield 81%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 15.8 (d, Pcy.sub.2), JPP 34 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. characteristic signals 3.58 (t, 2H, J=7, CH.sub.2 --N), 7.6-7.9
(m, 4H, phthalimide).
1.24 g (1.48 mmol) of the orange powder and 0.3 ml of hydrazine hydrate in
12 ml of ethanol are heated at reflux for 2 hours. After cooling, 25 ml of
methylene chloride are added and the suspension is filtered and washed.
The solution is concentrated in a rotary evaporator under reduced pressure
and the product is purified by chromatography (eluant MeOH with 2%
triethylamine). 0.98 g of orange, almost solid oil of the compound of
formula 8 is obtained (yield 94%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 15.7 (d, Pcy.sub.2). JPP 33 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. characteristic signals 2.6 (t, 2H, J=7, CH.sub.2 --N).
EXAMPLE A9
Synthesis of the Liqand of Formula 9 Immobilisable on Organic Carriers
##STR24##
0.24 ml (0.9 mmol) of 1-triethoxysilyl-3-isocyanatopropane is added
dropwise to a solution of 506 mg (0.71 mmol) of the compound of formula 8
from Example 8 in 10 ml of methylene chloride and the mixture is stirred
at room temperature overnight. The solvent is then evaporated off in a
rotary evaporator under reduced pressure and the crude product is purified
by chromatography (eluant: ethyl acetate). 530 mg of an orange, viscous
foam of the compound of formula 7c are obtained (yield 72%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 15.7 (d, Pcy.sub.2), JPP 33 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 1.22 (t, J=7, 9H, O--CH.sub.2 --CH.sub.3), 2.95-3.25 (m, 4H,
CH.sub.2 --NH--C(O)--NH--CH.sub.2), 3.81 (q, J=7, 6H, O--CH.sub.2).
EXAMPLE A10
Preparation of the Compound of Formula 10
Preparation of
(R)-N,N-dimethyl-1-[1'-(bromo)-(S)-2-diphenylphosphino-ferrocenyl]ethyl-di
xylylphosphine
##STR25##
6.75 g (13 mmol) of the compound of formula 4 and 3.2 g of
bis(3,5-xylyl)phosphine (13.2 mmol) in 5 ml of toluene are stirred in 80
ml of acetic acid at 100.degree. C. (bath temperature) for 4 hours. After
cooling, the reaction mixture is concentrated to dryness in vacuo in a
rotary evaporator at 40-50.degree. C. and then purified by chromatography
(silica gel: Merck 60; eluant: hexane/ethyl acetate 20/1). 7.7 g of
product are obtained (yield 82%, orange powder).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.45 (t, 3H, C--CH.sub.3),
2.20 and 2.28 (each 1 s, 12H, Ph--CH.sub.3), 3.45-4.3 (m, 7H, C.sub.5
H.sub.3 FeC.sub.5 H.sub.4 and 1H, CH--CH.sub.3), 6.75-7.7 (m, 16H,
P(C.sub.6 H.sub.5).sub.2 and P(C.sub.6 H.sub.3 Me.sub.2) .sup.31 P--NMR
(CDCl.sub.3): .delta. 7.75 (d, Pxylyl.sub.2), -26.4 (d, PPh.sub.2), JPP 22
Hz.
EXAMPLE A11
Preparation of the Compound of Formula 11
(R)-N,N-Dimethyl-1-[1'-(bromo)-(S)-2-diphenylphosphino-ferroceny]ethyldiphe
nyl-phosphine
##STR26##
2.03 g (3.9 mmol) of the compound of formula 4 and 0.8 ml of
diphenylphosphine (4.5 mmol) are stirred in 20 ml of acetic acid at
100.degree. C. (bath temperature) for 4 hours. After cooling, 50 ml of
water are added to the orange solution and the mixture is repeatedly
extracted by shaking with toluene. The organic phases are collected,
washed with water, dried with Na.sub.2 SO.sub.4 and concentrated in a
rotary evaporator. The orange crude product is purified by chromatography
(silica gel: Merck 60; eluant: hexane/ethyl acetate 30/1). 2.1 g of
product are obtained (yield 81%, orange powder).
Analysis: .sup.1 H--NMR (CDCl.sub.3): .delta. 1.45 (t, 3H, C--CH.sub.3),
3.5-4.3 (m, 7H, C.sub.5 H.sub.3 FeC.sub.5 H.sub.4 and 1H, CH--CH.sub.3),
7.1-7.38 (m, 20H, P(C.sub.6 H.sub.5).sub.2) .sup.31 P--NMR (CDCl.sub.3):
.delta. 7.12 (d, CH(Me)--PPh.sub.2, -27.18 (d, PPh.sub.2), JPP 25 Hz.
EXAMPLE A12
Preparation of the Compound of Formula 12
(R)-1-[1'-(1"-Dimethylsilyl-3"-chloropropyl)-(S)-2-(diphenylphosphino)ferro
cenyl]ethyldi-3,5-xylylphosphine starting from the compound of formula (10)
from Example 10.
##STR27##
2.5 mmol of a 1.6 M BuLi solution in hexane are added dropwise at -40 to
-30.degree. C., with stirring, to a solution of 1 g (1.9 mmol) of the
compound of formula (10) in 18 ml of diethyl ether. The mixture is then
cooled to -78.degree. C. and 460 mg (2.69 mmol) of
3-chloropropyl-dimethylchlorosilane are slowly added. The mixture is then
allowed to rise slowly to room temperature and is then stirred for a
further 1 hour. 20 ml of water are then added and the reaction mixture is
repeatedly extracted by shaking with CH.sub.2 Cl.sub.2. The organic phases
are collected, washed with water, dried with Na.sub.2 SO.sub.4 and
concentrated in a rotary evaporator. The orange crude product is purified
by chromatography (silica gel: Merck 60; eluant: hexane/diethyl ether
30/1). 1.1 g of the compound of formula (10) are obtained (yield 75%,
orange powder).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -26.5 (d,
PPh.sub.2), 6.7 (d, Pxyl.sub.2), JPP 21 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 0.04 (s, 3H, Si--CH.sub.3), 0.14 (s, 3H, Si--CH.sub.3), 0.6 (m,
2H, CH.sub.2 --Si), 1.43 (d, 3H, CH--CH.sub.3), 1.5-1.7 (m, 2H, CH.sub.2
--CH.sub.2 --Cl), 2.20 and 2.30 (two s, each 6H, C.sub.6 H.sub.3
(CH.sub.3).sub.2, 3.41 (t, 2H, J=7, CH.sub.2 --Cl), 3.2-4.5 (m, 8H,
C.sub.5 H.sub.4 FeC.sub.5 H.sub.3 CH), 6.7-7.8 (m, 16H, P(C.sub.6
H.sub.5).sub.2 and P(C.sub.6 H.sub.3 Me.sub.2).sub.2).
EXAMPLE A13
Preparation of the Compound of Formula 13
The primary amine of formula 13 is prepared by way of Gabriel synthesis
(conversion of the chloride into the phthalimide and freeing of the amine
with hydrazine hydrate):
##STR28##
464 mg of potassium phthalimide (2.5 mmol) and 125 mg of
hexadecyltributyl-phosphonium bromide (catalyst) are added to a solution
of 1.53 g (2 mmol) of the compound of formula 12 in 4 ml of DMF and the
mixture is stirred at 100.degree. C. (bath temperature) for 2 hours. After
cooling, the mixture is extracted by shaking in water/toluene and the
organic phase is dried with sodium sulfate and concentrated in a rotary
evaporator. After purification by chromatography (silica gel: Merck 60;
eluant: hexane/ethyl acetate 9/1), 1.58 g of phthalimide are obtained in
the form of an orange powder (yield 90%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -25.3 (d,
PPh.sub.2), 7.0 (d, Pxyl.sub.2), JPP 21 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 0.04 (s, 3H, Si--CH.sub.3), 0.1 (s, 3H, Si--CH.sub.3), 0.5 (m, 2H,
CH.sub.2 --Si),1.44 (m, 3H, CH--CH.sub.3), 1.4-1.7 (m, 2H, CH.sub.2
--CH.sub.2 --N), 2.20 and 2.27 (two s, each 6H, C.sub.6 H.sub.3
(CH.sub.3).sub.2), 3.58 (t, 2H, J=7, CH.sub.2 --N), 3.2-4.4 (m, 8H,
C.sub.5 H.sub.4 FeC.sub.5 H.sub.3 CH), 6.7-7.8 (m, 16H, P(C.sub.6
H.sub.5).sub.2), P(C.sub.6 H.sub.3 (Me).sub.2), 7.6-7.9 (m, 4H,
phthalimide).
1.58 g (1.78 mmol) of the phthalimide obtained in the first step and 0.5 ml
of hydrazine hydrate in 20 ml of ethanol are boiled at reflux for 2 hours.
After cooling, 50 ml of toluene are added and the suspension is filtered
and washed with 2.times.10 ml of water. The solution is dried with sodium
sulfate and concentrated in a rotary evaporator under reduced pressure;
the product is again made into a suspension with 20 ml of diethyl ether
and filtered. After concentration in a rotary evaporator, 1.34 g of an
orange foam are obtained (yield 99%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -25.2 (d,
PPh.sub.2), 6.7 (d, Pxyl.sub.2), JPP 22 Hz. .sup.1 H--NMR (CDCl.sub.3):
.delta. 0.03 (s, 3H, Si--CH.sub.3), 0.11 (s, 3H, Si--CH.sub.3), 0.48 (m,
2H, CH.sub.2 --Si), 1.15-1.45 (m, 2H, CH.sub.2 --CH.sub.2 --N), 1.45 (m,
3H, CH--CH.sub.3), 2.20 and 2.27 (two s, each 6H, C.sub.6 H.sub.3
(CH.sub.3).sub.2), 2.58 (t, 2H, J=7, CH.sub.2 --N), 3.2-4.45 (m, 8H,
C.sub.5 H.sub.4 FeC.sub.5 H.sub.3 CH), 6.7-7.75 (m, 16H, P(C.sub.6
H.sub.5).sub.2), P(C.sub.6 H.sub.3 (Me).sub.2).
EXAMPLE A14
Preparation of the Compound of Formula 14
Synthesis of the ligand of formula (14) immobilisable on inorganic carriers
##STR29##
0.7 ml (2.6 mmol) of 1-triethoxysilyl-3-isocyanatopropane is added dropwise
to a solution of 1.5 g (1.99 mmol) of the compound of formula (13) in 10
ml of methylene chloride and the mixture is stirred overnight at room
temperature. The solvent is then evaporated off in a rotary evaporator
under reduced pressure and the crude product is purified by chromatography
(silica gel: Merck 60, eluant: hexane/ethyl acetate). 1.47 g of an orange,
viscous foam are obtained (yield 74%).
Characterisation: .sup.31 P--NMR (CDCl.sub.3): .delta. -25.2 (d,
PPh.sub.2), 6.7 (d, Pxyl.sub.2), JPP 21 Hz. .sup.1 H--NMR (CDCl.sub.3)
characteristic signals: .delta. 0.03 (s, 3H, Si--CH.sub.3), 0.11 (s, 3H,
Si--CH.sub.3), 0.48 (m, 2H, CH.sub.2 --Si-cp), 0.61 (m, 2H, CH.sub.2
--Si(OEt).sub.3), 1.2-1.8 (m, 4H, CH.sub.2 CH.sub.2 NHCONHCH.sub.2
CH.sub.2), 1.22 (t, J=7, 9H, O--CH.sub.2 --CH.sub.3), 1.47 (m, 3H,
CH--CH.sub.3), 2.20 and 2.28 (two s, each 6H, C.sub.6 H.sub.3
(CH.sub.3).sub.2), 2.95-3.25 (m, 4H, CH.sub.2 --NHCONH--CH.sub.2), 3.83
(q, J=7, 6H, O--CH.sub.2), 6.7-7.8 (m, 16H, P(C.sub.6 H.sub.5).sub.2),
P(C.sub.6 H.sub.3 (Me).sub.2). Mass spectrum: 1001 (M+H.sup.+).
EXAMPLE B
Ligands Immobilised on Silica Gel or Polystyrene
Examples B1-B3 Ligands immobilised on silica gel.
Immobilisation: Before use the carrier is dried at 130.degree. C. for 3
hours under a high vacuum and then placed under argon. Then a solution of
immobilisable ligand of formula 9 from Example A9 or of formula 14 from
Example A14 in toluene is added and the mixture is stirred at
85-90.degree. C. for 20 hours. After cooling and settling, the supernatant
solution is drawn off using a syringe. The mixture is then washed six
times with MeOH (7 ml per g of carrier each time) and finally dried at
40-50.degree. C. under a high vacuum. The results are given in Table 1.
TABLE 1
__________________________________________________________________________
Immobilis- Amount
Analysis
Loading
able ligand
Amount
Carrier
Amount
toluene
P content
mmol ligand
No.
No. [mg]
type [g] [ml] [%] per g carrier
__________________________________________________________________________
B1 9 238 Grace 332
2.2 9.8 0.1 0.098
B2 9 100 Grace 332
2.2 9.8 0.26 0.041
B3 14 300 Grace 332
3.0 24.0 0.33 0.052
__________________________________________________________________________
The carrier used is supplied by the W. R. Grace company: Grace 332: spec.
surface=320 m.sup.2 /g, particle size=35-70 micrometers.
Example B4 Ligands immobilised on polystyrene
In a vessel having a stirrer and a glass frit, 900 mg of polymer
(aminomethylated poly-styrene, crosslinked with 1% divinyl benzene, amine
content=0.56 mmol/g, supplied by: Novabiochem, 01-64-0010), which has been
dried under a high vacuum at 50.degree. C., are stirred in 32 ml of
methylene chloride until the carrier has swelled. Then 1.2 ml (8.3 mmol)
of 2,4-toluylene diisocyanate (TDI) are rapidly added and the mixture is
stirred for a further 1 hour. The excess TDI is then removed by filtering
off the solution and washing five times with 30 ml of methylene chloride.
The carrier that has reacted with the TDI is then stirred in 30 ml of
methylene chloride, and a solution of 100 mg (0.133 mmol) of the compound
of formula (13) from Example A13 in 2 ml of methylene chloride is added
dropwise thereto. The mixture is stirred overnight. In order to convert
residual isocyanate groups into carbamates; 10 ml of ethyl alcohol
containing 30 .mu.l of triethylamine are added as catalyst and the mixture
is stirred overnight at 40.degree. C. The yellowish-orange carrier is then
filtered off and washed five times using 20 ml of methylene chloride each
time. Finally the carrier is dried under a high vacuum.
Analysis: P content=0.62%. This corresponds to a loading of 0.1 mmol of
ligand per g of carrier.
EXAMPLE C1
Hydrogenations
General: All operations are cared out under inert gas. The 50 ml steel
autoclave is equipped with a magnetic stirrer (1500 rev/min) and a flow
interrupter. Prior to each hydrogenation the inert gas in the autoclave is
displaced by hydrogen in 4 cycles (10 bar, normal pressure). Then the
desired hydrogen pressure is established in the autoclave and the
hydrogenation is started by switching on the stirrer. The conversion is
determined by gas chromatography and the optical yield is determined by
means of HPLC (column: Chiracel OD), there being used for that purpose a
sample that has been purified by flash chromatography (silica gel: Merck
60, eluant=hexane/ethyl acetate).
EXAMPLE C1
A solution of 4.06 mg of [Rh(COD).sub.2 ]BF.sub.4 in 3.3 ml of methanol is
added to 122 mg of ligand from Example B1 (ligand 9) and the mixture is
stirred slowly, the yellow solution being completely decolourised. Then
554 mg of substrate
(N-(2',6'-dimethylphen-1'-yl)-N-(methoxyacetyl)-1-methoxycarbonyl-ethenyla
mine) dissolved in 5 ml of methanol are added and the mixture is heated to
40.degree. C. in an oil bath and hydrogenated that temperature. After 1
hour, the reaction is discontinued and the hydrogen in the hydrogenation
flask is replaced by inert gas. The catalyst is allowed to settle and the
supernatant solution is drawn off using a syringe. The conversion is
complete and the optical yield is 82.2% (R).
EXAMPLE C2
A solution of 3.5 mg of [Ir(COD)Cl].sub.2 (0.0104 mmol Ir) in 2 ml of THF
is added all at once to 250 mg (0.013 mmol) of ligand from Example B3
fixed to silica gel and the mixture is stirred slowly, the yellow solution
being completely decolourised. The catalyst is then allowed to settle and
the supernatant THF is drawn off using a syringe and the catalyst is dried
under a high vacuum. 10 mg of tetrabutylammonium iodide and finally 4.25 g
(20.8 mmol) of imine are added to a second flask, the solution is placed
under inert gas and added to the catalyst. The reaction mixture is then
introduced under pressure into a 50 ml steel autoclave using a steel
capillary against a current of inert gas and then hydrogenated at
25.degree. C. at a hydrogen pressure of 80 bar. After 2 hours the hydrogen
is depressurised and the catalyst is filtered off under argon. The
conversion is complete and the optical yield is 77.5% (S).
Re-use:
4.25 g (20.38 mmol) of imine and 10 mg of tetrabutylammonium iodide are
added all at once to the separated catalyst. The reaction mixture is then
introduced under pressure into a 50 ml steel autoclave using a steel
capillary against a current of inert gas and then hydrogenated at
25.degree. C. at a hydrogen pressure of 80 bar. After 2 hours, the
hydrogen is depressurised and the catalyst is filtered off under argon.
The conversion is complete and the optical yield is 77.8% (S).
EXAMPLE C3
60 mg (0.006 mmol) of polymer-bonded Xyliphos from Example B4 are added all
at once and stirred in 2 ml of THF for 5 minutes. Then a solution of 1.7
mg of [Ir(COD)Cl].sub.2 (0.005 mmol Ir) in 2 ml THF is added and the
mixture is stirred slowly, the yellow solution being decolorised. 5 mg of
tetrabutylammonium iodide and 2.1 g (10.2 mmol) of
N-(2'-methyl-6'-ethyl-phen-1'-yl)-N-(1-methoxymethyl)-ethylimine are added
to a second flask, the solution is placed under inert gas and added to the
catalyst. The reaction mixture is then introduced under pressure into a 50
ml steel autoclave using a steel capillary against a current of inert gas
and then hydrogenated at 25.degree. C. at a hydrogen pressure of 80 bar.
After 16 hours the hydrogenation is discontinued, the hydrogen is
depressurised and the catalyst is filtered off. The conversion is 68%
after that time and the optical yield is 71.1%(S).
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